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Med1 controls thymic T-cell migration into lymph node through enhancer-based Foxo1-Klf2 transcription program.

Ning Yuan1,2, Yanhong Su1,2, Yang Gao1,2,3,4

  • 1Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

European Journal of Immunology
|July 29, 2024
PubMed
Summary

Mediator complex component Med1 is crucial for T-cell migration to lymph nodes. It regulates enhancer-based Foxo1-Klf2 transcription, essential for T-cell homing and immune surveillance.

Keywords:
Klf2 • Lymph nodes • Med1 • Migration • T cell

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • T-cell migration is vital for immune surveillance.
  • Promoter-based regulation of T-cell migration is known, but enhancer roles are unclear.

Purpose of the Study:

  • To investigate the role of enhancers in T-cell migration.
  • To explore the function of Med1 in T-cell migration and immune surveillance.

Main Methods:

  • Conditional deletion of Med1 in thymic T cells.
  • Analysis of T-cell populations in circulation, lymph nodes, and spleen.
  • Quantitative PCR and flow cytometry to assess gene and protein expression.
  • Chromatin immunoprecipitation to study transcription factor binding.

Main Results:

  • Med1 deletion reduced CD4+ and CD8+ T cells in lymph nodes and CD8+ T cells in the spleen.
  • Med1 deficiency impaired thymic αβT-cell migration to circulation and lymph nodes.
  • Med1 deletion led to downregulation of KLF2, CCR7, and CD62L.
  • Med1 facilitates Foxo1 binding to the Klf2 enhancer, promoting Klf2 transcription.
  • Forced Klf2 expression rescued T-cell migration and expression of downstream genes.

Conclusions:

  • Med1 plays a critical role in regulating T-cell migration to lymph nodes.
  • Med1 controls T-cell homing via an enhancer-based Foxo1-Klf2 transcriptional program.
  • This study provides insights into the molecular mechanisms of T-cell migration.